Evaluation of the ability of insulin resistance and lipid-related indices to predict the presence of NAFLD in obese adolescents.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has become an important health issue in adolescents. Although several parameters and indices have been investigated for the evaluation of NAFLD in adults, these indices are limited in adolescents. In this study, body mass index, waist circumference, triponderal mass index, HbA1c, homeostatic model assessment insulin resistance (HOMA-IR), triglyceride/high-density lipoprotein (Tg/HDL), the lipid accumulation product (LAP) index, the triglyceride-glucose (TyG) index and the aminotransferase (AT) index were examined together, and their diagnostic values in the clinical treatment of NAFLD were compared. MATERIALS AND METHODS: Seventynine adolescents (10-19 years old) with obesity who were admitted to a pediatric clinic between January and August 2022 and who were diagnosed with exogenous obesity without any comorbidities were included in the study. The presence of NAFLD was evaluated by liver magnetic resonance imaging. The laboratory findings were obtained retrospectively from system records. Parameters were compared between the NAFLD (+) and NAFLD (-) groups. Logistic regression analysis was used to determine the most effective factors for NAFLD treatment. Receiver operating characteristic (ROC) analysis was performed with significant indices. Sex, HOMA-IR, TyG and AT indices were evaluated together with multivariate analysis to design a diagnostic scale. RESULTS: HbA1c, HOMA-IR, AT indices and TyG indices were greater in the NAFLD (+) group (P = 0.012; P = 0.001; P = 0.012; P = 0.002, respectively). There was a positive correlation between liver fat percentage and HOMA-IR, the TyG index, the AT index, and Tg/HDL. According to the regression analysis, male sex and elevated HOMA-IR were determined to be significant risk factors for the presence of NAFLD. A probability scale with 4 parameters [sex, HOMA-IR, the TyG index, and alanine aminotransferase (ALT)] was designed with 82.5% specificity and 80% sensitivity. CONCLUSION: Evaluation of the HOMA-IR and TyG indices, especially in high-risk patients, will support the diagnosis of NAFLD via ultrasonography. A probability scale with ALT, HOMA-IR, TyG, and sex data with a diagnostic accuracy of 80% may aid in the diagnosis of NAFLD in adolescents with obesity.

Non-diabetic elderly populations: the MHR as a protective factor against bone abnormalities.

Objectives: In China, osteoporosis has become a major health concern among elderly population, imposing significant burden on the country's social and economic systems. The monocyte to high-density lipoprotein ratio (MHR) has been currently recommended as a novel marker of inflammation and oxidative stress associated with osteoporosis in type 2 diabetes mellitus (T2DM). However, its reliability in non-diabetic elderly populations remains unclear. The present study was to evaluate the association between MHR and osteoporosis in a non-diabetic elderly population. Methods: The clinical data of 240 non-diabetic elderly subjects (115 in the osteoporosis group and 125 in the normal bone group) were retrospectively analyzed and all statistical analyses were performed by using SPSS 26.0. Results: Differences in age, neutrophils, lymphocytes, monocytes, MHR, uric acid, creatinine, triglycerides,and high-density lipoprotein cholesterol were found to be statistically significant between the two groups. A binary logistic regression model was conducted by including age, MHR, UA and Cr as variables. The results showed that age was an independent risk factor and MHR was an independent protective factor for bone abnormality in the non-diabetic elderly population. The ROC analysis showed that the area under the curve for the predictive effect of MHR, age and their combined test on osteoporosis in non-diabetic elderly populations was 0.623, 0.728 and 0.761, respectively; the correlation analysis showed that MHR was positively correlated with lumbar and hip BMD, and negatively associated with femoral neck stress ratio, femoral intertrochanteric stress ratio, and femoral stem stress ratio, showing statistically significant differences (P<0.05). Conclusions: For the non-diabetic elderly population: the MHR is a protective factor against bone abnormalities and was significantly higher in the normal bone group than in the abnormal bone group.

Imbalance of APOB Lipoproteins and Large HDL in Type 1 Diabetes Drives Atherosclerosis.

BACKGROUND: Individuals with type 1 diabetes (T1D) generally have normal or even higher HDL (high-density lipoprotein)-cholesterol levels than people without diabetes yet are at increased risk for atherosclerotic cardiovascular disease (CVD). Human HDL is a complex mixture of particles that can vary in cholesterol content by >2-fold. To investigate if specific HDL subspecies contribute to the increased atherosclerosis associated with T1D, we created mouse models of T1D that exhibit human-like HDL subspecies. We also measured HDL subspecies and their association with incident CVD in a cohort of people with T1D. METHODS: We generated LDL receptor-deficient (Ldlr-/-) mouse models of T1D expressing human APOA1 (apolipoprotein A1). Ldlr-/-APOA1Tg mice exhibited the main human HDL subspecies. We also generated Ldlr-/-APOA1Tg T1D mice expressing CETP (cholesteryl ester transfer protein), which had lower concentrations of large HDL subspecies versus mice not expressing CETP. HDL particle concentrations and sizes and proteins involved in lipoprotein metabolism were measured by calibrated differential ion mobility analysis and targeted mass spectrometry in the mouse models of T1D and in a cohort of individuals with T1D. Endothelial transcytosis was analyzed by total internal reflection fluorescence microscopy. RESULTS: Diabetic Ldlr-/-APOA1Tg mice were severely hyperglycemic and hyperlipidemic and had markedly elevated plasma APOB levels versus nondiabetic littermates but were protected from the proatherogenic effects of diabetes. Diabetic Ldlr-/-APOA1Tg mice expressing CETP lost the atheroprotective effect and had increased lesion necrotic core areas and APOB accumulation, despite having lower plasma APOB levels. The detrimental effects of low concentrations of larger HDL particles in diabetic mice expressing CETP were not explained by reduced cholesterol efflux. Instead, large HDL was more effective than small HDL in preventing endothelial transcytosis of LDL mediated by scavenger receptor class B type 1. Finally, in humans with T1D, increased concentrations of larger HDL particles relative to APOB100 negatively predicted incident CVD independently of HDL-cholesterol levels. CONCLUSIONS: Our results suggest that the balance between APOB lipoproteins and the larger HDL subspecies contributes to atherosclerosis progression and incident CVD in the setting of T1D and that larger HDLs exert atheroprotective effects on endothelial cells rather than by promoting macrophage cholesterol efflux.

[Correlation between serum HDL/LDL and t-PINP /ß-CTX and osteoporotic vertebral fractures in elderly women].

OBJECTIVE: To explore high density lipoprotein (HDL)/low density lipoprotein (LDL) and total typeⅠcollagen amino terminal extender peptide (t-PINP)/ C-terminal peptide of typeⅠcollagen ß special sequence(ß-CTX)and risk of osteoporosis vertebral fractures (OPVFs) in elderly women. METHODS: The clinical data of 446 female OPVFs patients aged above 60 years old from January 2019 to December 2020 were retrospectively analyzed. According to whether or not fracture, patients were divided into non-fracture group (186 patients) and fracture group(260 patients). Univariate analysis was performed to analysis age, body mass index(BMI), N-terminal mioldle molecular fragment of osteocalcin, N-MID OC), t-PINP, ß-CTX, 25-hydroxyvitamin D[25-(OH) VitD], blood sugar (Glu), total cholesterol(TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), Ca, P, Mg, urea (UREA), creatinine (Cr) and Cystatin C(CysC), and correlation between OPVFs and the above indexes and lipid, bone metabolism indexes between two groups;Logistic regression was performed to analyze risk factors and stratification relationship between vertebral fracture and HDL/LDL, t-PINP/ß-CTX. Logistic regression was used to analyze risk factors and stratification relationship between OPVFs and HDL/LDL, t-PINP/ß-CTX. RESULTS: There were no significant difference in age and BMI between non-fracture group and fracture group (P>0.05). Compared with non-fracture group, contents of HDL, t-PINP/ß-CTX and HDL/LDL in fracture group were decreased, and contents of ß-CTX were increased (P<0.05). OPVFs was positively correlated with ß-CTX (r=0.110, P<0.05), and negatively correlated with HDL, HDL/LDL and t-PINP/ß-CTX (r=-0.157, -0.175, -0.181, P<0.05). HDL and HDL/LDL were negatively correlated with ß-CTX (r=-0.22, -0.12, P<0.05) and t-PINP (r=-0.13, -0.10, P<0.05). 25-(OH) VitD was positively correlated with TC and HDL (r=0.11, 0.18, P<0.05). HDL/LDL was positively correlated with t-PINP/ß-CTX(r=0.11, P=0.02). t-PINP/ß-CTX[OR=0.998, 95%CI(0.997, 1.000), P<0.05], HDL/LDL[OR=0.228, 95%CI(0.104, 0.499), P<0.01] were risk factors for vertebral fracture. The lower levels between two tristratified indicators, the higher the vertebral fracture rate. The risk of fracture was 2.5 and 2 times higher in the lowest stratum than in the highest stratum, with an adjusted OR was[2.112, 95%CI(1.310, 3.404)] and [2.331, 95%CI(1.453, 3.739)], respectively. CONCLUSION: Serum low HDL/LDL and t-PINP /ß-CTX are independent risk factors for OPVF in elderly women, and have good predictive value for OPVF risk.

Nomogram incorporating preoperative pan-immune-inflammation value and monocyte to high-density lipoprotein ratio for survival prediction in patients with colorectal cancer: a retrospective study.

OBJECTIVE: Using the preoperative pan-immune-inflammation value (PIV) and the monocyte to high-density lipoprotein ratio (MHR) to reflect inflammation, immunity, and cholesterol metabolism, we aim to develop and visualize a novel nomogram model for predicting the survival outcomes in patients with colorectal cancer (CRC). METHODS: A total of 172 patients with CRC who underwent radical resection were retrospectively analyzed. Survival analysis was conducted after patients were grouped according to the optimal cut-off values of PIV and MHR. Univariate and multivariate analyses were performed using Cox proportional hazards regression to screen the independent prognostic factors. Based on these factors, a nomogram was constructed and validated. RESULTS: The PIV was significantly associated with tumor location (P < 0.001), tumor maximum diameter (P = 0.008), and T stage (P = 0.019). The MHR was closely related to gender (P = 0.016), tumor maximum diameter (P = 0.002), and T stage (P = 0.038). Multivariate analysis results showed that PIV (Hazard Ratio (HR) = 2.476, 95% Confidence Interval (CI) = 1.410-4.348, P = 0.002), MHR (HR = 3.803, 95%CI = 1.609-8.989, P = 0.002), CEA (HR = 1.977, 95%CI = 1.121-3.485, P = 0.019), and TNM stage (HR = 1.759, 95%CI = 1.010-3.063, P = 0.046) were independent prognostic indicators for overall survival (OS). A nomogram incorporating these variables was developed, demonstrating robust predictive accuracy for OS. The area under the curve (AUC) values of the predictive model for 1-, 2-, and 3- year are 0.791,0.768,0.811, respectively. The calibration curves for the probability of survival at 1-, 2-, and 3- year presented a high degree of credibility. Furthermore, Decision curve analysis (DCA) for the probability of survival at 1-, 2-, and 3- year demonstrate the significant clinical utility in predicting survival outcomes. CONCLUSION: Preoperative PIV and MHR are independent risk factors for CRC prognosis. The novel developed nomogram demonstrates a robust predictive ability, offering substantial utility in facilitating the clinical decision-making process.

The indicative effects of apolipoproteins on organic erectile dysfunction: bridging Mendelian randomization and case-control study.

The existing research on the association between apolipoproteins (Apos) and erectile dysfunction (ED) primarily relies on observational studies and does not distinguish between organic and psychogenic causes when diagnosing ED. It is difficult to believe that Apos play a role in psychogenic ED. To address these issues, our study explored the causal relationship between lipoproteins and ED using Mendelian randomization (MR) analysis and differentiate between organic and psychogenic ED through the use of nocturnal penile tumescence and rigidity (NPTR) monitoring. Multivariate MR analysis revealed significant causal associations between high-density lipoprotein (HDL), Apo A1, and Apo B/A1 with ED (OR and 95% CI were 0.33 (0.14-0.78), 3.58 (1.52-8.43), and 0.30 (0.13-0.66)). we conducted statistical and analytical analyses on the data of 212 patients using multivariate analyses and receiver operating characteristic (ROC) curves. Patients with organic ED had significantly lower levels of HDL, Apo A1 and Apo A1/B, whereas patients with organic ED had considerably higher levels of Apo B and low-density lipoprotein (LDL). The diagnostic value of Apos in predicting the risk of organic ED was evaluated using ROC curves. The results indicated that Apo A1 and Apo A1/B demonstrated good predictive value. HDL, Apo A1, and Apo A1/B have been identified as risk factors for ED in our study. Furthermore, our research highlights the significance of Apo A1 and Apo A1/Apo B in the development of organic ED and suggests their potential use as indicators to assess the risks associated with organic ED.

Evaluation of alanine aminotransferase/aspartate aminotransferase ratio and high-density lipoprotein for predicting neonatal adverse outcomes associated with intrahepatic cholestasis of pregnancy.

Background: To determine the association between lipid metabolism and intrahepatic cholestasis of pregnancy (ICP), and explore the value of maternal alanine aminotransferase/aspartate aminotransferase (ALT/AST) and high-density lipoprotein (HDL) in predicting adverse neonatal outcomes in women with ICP. Methods: A total of 147 pregnant women with ICP admitted to The Fourth Hospital of Shijiazhuang and 120 normal pregnant women in the same period were selected in this study. The Mann-Whitney U test and Chi-square tests were used to compare the differences in clinical data. Multivariate logistic regression was used to analyze the relationship between ALT/AST and the occurrence of adverse pregnancy outcomes in patients with ICP. The combined predictive value of ALT/AST and HDL was determined by receiver operating characteristic (ROC) curve analysis. Results: Among 147 women with ICP, 122 women had total bile acid (TBA) levels of 10-39.9 µmol/L, and 25 had TBA ≥ 40 µmol/L. There was significantly lower gestational age in patients with severe ICP than in those with mild and control groups (all p < 0.05), and the weight of newborns in the maternal ICP group was significantly lower than in the control group (p < 0.05). Increasing TBA levels was associated with higher AST, ALT, ALT/AST, and lower HDL level (all p < 0.05). Meanwhile, higher levels of ALT/AST was positively associated with neonatal hyperbilirubinemia [adjusted odds ratio (AOR) = 4.019, 95% CI [1.757-9.194, p = 0.001] and cardiac injury [AOR = 3.500, 95% CI [1.535-7.987], p = 0.003]. HDL was a significant protective factor for neonatal hyperbilirubinemia and cardiac injury [AOR = 0.315, 95% CI [0.126-0.788], p = 0.014; AOR = 0.134 (0.039-0.461), p = 0.001]. The area under the ROC curve (AUC) for prediction of neonatal hyperbilirubinemia by ALT/AST combined with HDL was 0.668 [95% CI [56.3-77.3%], p = 0.002], and the sensitivity and specificity were 47.1% and 84.0%, respectively. To predict neonatal cardiac injury, the AUC value was 0.668 [95% CI [56.4-77.1%], p = 0.002], with sensitivity and specificity were 41.2% and 87.1%, respectively. Conclusions: The levels of higher ALT/AST and lower HDL were significantly associated with the risk of ICP-related adverse neonatal outcomes. Moreover, ALT/AST combined with HDL has moderate clinical value in predicting the adverse outcomes of neonatal hyperbilirubinemia and cardiac injury.

High-density lipoprotein infusion therapy: A review.

Increased cholesterol-rich, low-density, non-calcified atheromas as assessed by computer coronary tomography angiography analyses have been shown to predict myocardial infarction significantly better than coronary artery calcium score or the presence of obstructive coronary artery disease (CAD) as evaluated with standard coronary angiography. Low serum high-density lipoprotein (HDL) cholesterol values are an independent risk factor for CAD. Very small, lipid-poor preß-1 HDL particles have been shown to be most effective in promoting cellular cholesterol efflux. HDL infusions have been documented to reduce aortic atherosclerosis in cholesterol-fed animal models. However, human studies using infusions of either the HDL mimetic containing recombinant apolipoprotein (apo) A-I Milano or Cerenis Compound-001 with native recombinant apoA-I have been mainly negative in promoting coronary atherosclerosis progression as assessed by intravascular ultrasound. In contrast, a study using 7 weekly infusions of autologous delipidated HDL in six homozygous familial hypercholesterolemic patients was effective in promoting significant regression of low-density non-calcified coronary atheroma regression as assessed by computed coronary angiography. This therapy has received Food and Drug Administration approval. Commonwealth Serum Laboratories has carried out a large clinical endpoint trial using an HDL complex (native apoA-I with phospholipid), and the results were negative. Our purpose is to review animal and human studies using various forms of HDL infusion therapy to promote regression of atherosclerosis. In our view, differences in results may be due to: 1) the HDL preparations used, 2) the subjects studied, and 3) the methods used to assess coronary atherosclerosis.

High-density lipoprotein metrics during midlife and future subclinical atherosclerosis in women: the SWAN HDL study.

OBJECTIVE: The clinical utility of high-density lipoprotein cholesterol (HDL-C) in risk classification is limited, especially in midlife women. Novel metrics of HDL may better reflect this risk. We clustered a comprehensive profile of HDL metrics into favorable and unfavorable clusters and assessed how these two clusters are related to future subclinical atherosclerosis (carotid intima media thickness [cIMT], interadventitial diameter [IAD], and carotid plaque presence) in midlife women. METHODS: Four hundred sixty-one women (baseline age: 50.4 [2.7] years; 272 White, 137 Black, 52 Chinese) from the Study of Women's Health Across the Nation HDL ancillary study who had baseline measures of HDL cholesterol efflux capacity (HDL-CEC), lipid contents (HDL-phospholipids [HDL-PL] and HDL triglycerides [HDL-Tg]), and HDL particle (HDL-P) distribution and size, followed by carotid ultrasound (average 12.9 [SD: 2.6] years later), were included. Using latent cluster analysis, women were clustered into a favorable (high HDL-CEC, HDL-PL, large and medium HDL-P, less HDL-Tg and small HDL-P, larger size) or an unfavorable HDL cluster (low HDL-CEC, HDL-PL, large and medium HDL-P, more HDL-Tg, and small HDL-P, smaller size) and then linked to future subclinical atherosclerosis using linear or logistic regression. RESULTS: The favorable HDL cluster was associated with lower cIMT, IAD, and odds of carotid plaque presence. These associations were attenuated by body mass index, except in Chinese women where the association with cIMT persisted (0.72 [0.63, 0.83]). CONCLUSIONS: The association between favorable HDL clusters and a better postmenopausal subclinical atherosclerosis profile is largely explained by body mass index; however, racial/ethnic differences may exist.

Association of High-Density Lipoprotein Parameters and Risk of Heart Failure: A Multicohort Analysis.

BACKGROUND: High-density lipoprotein (HDL) is commonly characterized by its cholesterol concentration (HDL-C) and inverse association with atherosclerotic cardiovascular disease. OBJECTIVES: The authors sought to evaluate the association of HDL particle concentration (HDL-P), HDL particle size (HDL-size), HDL-C, and cholesterol content per particle (HDL-C/HDL-P) with risk of overall heart failure (HF) and subtypes. METHODS: Participants from the Atherosclerosis Risk In Communities Study, Dallas Heart Study, Multi-Ethnic Study of Atherosclerosis, and Prevention of Renal and Vascular End-stage Disease studies without HF history were included. Associations of HDL-P, HDL-size, HDL-C, and HDL-C/HDL-P with risk of overall HF, HF with reduced and preserved ejection fraction were assessed using adjusted Cox models. RESULTS: Among 16,925 participants (53.5% women; 21.8% Black), there were 612 incident HF events (3.6%) (HF with reduced ejection fraction, 309 [50.5%]; HF preserved ejection fraction, 303 [49.5%]) over median follow-up of 11.4 years. In adjusted models, higher HDL-P was significantly associated with lower HF risk (HR of highest vs lowest tertile of HDL-P: 0.76 [95% CI: 0.62-0.93]). Larger HDL-size was significantly associated with higher overall HF risk (HR of largest vs smallest tertile of HDL-size: 1.27 [95% CI: 1.03-1.58]). HF risk associated with HDL-P and HDL-size was similar for HF subtypes. In adjusted analyses, there was no significant association between HDL-C and HF risk. Higher HDL-C/HDL-P was significantly associated with higher overall HF risk (HR of highest vs lowest tertile of HDL-C/HDL-P: 1.29 [95% CI: 1.04-1.60]). CONCLUSIONS: Higher HDL-P was associated with a lower risk of HF. In contrast, larger HDL-size was associated with higher risk of HF and there was no significant association observed between HDL-C and HF risk after accounting for cardiovascular risk factors.

Serum Levels of Adiponectin Are Strongly Associated with Lipoprotein Subclasses in Healthy Volunteers but Not in Patients with Metabolic Syndrome.

Metabolic syndrome (MS) is a widespread disease in developed countries, accompanied, among others, by decreased adiponectin serum levels and perturbed lipoprotein metabolism. The associations between the serum levels of adiponectin and lipoproteins have been extensively studied in the past under healthy conditions, yet it remains unexplored whether the observed associations also exist in patients with MS. Therefore, in the present study, we analyzed the serum levels of lipoprotein subclasses using nuclear magnetic resonance spectroscopy and examined their associations with the serum levels of adiponectin in patients with MS in comparison with healthy volunteers (HVs). In the HVs, the serum levels of adiponectin were significantly negatively correlated with the serum levels of large buoyant-, very-low-density lipoprotein, and intermediate-density lipoprotein, as well as small dense low-density lipoprotein (LDL) and significantly positively correlated with large buoyant high-density lipoprotein (HDL). In patients with MS, however, adiponectin was only significantly correlated with the serum levels of phospholipids in total HDL and large buoyant LDL. As revealed through logistic regression and orthogonal partial least-squares discriminant analyses, high adiponectin serum levels were associated with low levels of small dense LDL and high levels of large buoyant HDL in the HVs as well as high levels of large buoyant LDL and total HDL in patients with MS. We conclude that the presence of MS weakens or abolishes the strong associations between adiponectin and the lipoprotein parameters observed in HVs and disturbs the complex interplay between adiponectin and lipoprotein metabolism.

HDL and plaque regression in a multiphase model of early atherosclerosis.

Atherosclerosis is a chronic disease of the arteries characterised by the accumulation of lipids and lipid-engorged cells in the artery wall. Early plaque growth is aggravated by the deposition of low density lipoproteins (LDL) in the wall and the subsequent immune response. High density lipoproteins (HDL) counterbalance the effects of LDL by accepting cholesterol from macrophages and removing it from the plaque. In this paper, we develop a free boundary multiphase model to investigate the effects of LDL and HDL on early plaque development. We examine how the rates of LDL and HDL deposition affect cholesterol accumulation in macrophages, and how this impacts cell death rates and emigration. We identify a region of LDL-HDL parameter space where plaque growth stabilises for low LDL and high HDL influxes, due to macrophage emigration and HDL clearance that counterbalances the influx of new cells and cholesterol. We explore how the efferocytic uptake of dead cells and the recruitment of new macrophages affect plaque development for a range of LDL and HDL influxes. Finally, we consider how changes in the LDL-HDL profile can change the course of plaque development. We show that changes towards lower LDL and higher HDL can slow plaque growth and even induce regression. We find that these changes have less effect on larger, more established plaques, and that temporary changes will only slow plaque growth in the short term.

Pleiotropic functions and clinical importance of circulating HDL-PON1 complex.

High density lipoprotein (HDL) functions are mostly mediated through a complex proteome, particularly its enzymes. HDL can provide a scaffold for the assembly of several proteins that affect each other's function. HDL particles, particularly small, dense HDL3, are rich in paraoxonase 1 (PON1), which is an important enzyme in the functionality of HDL, so the antioxidant and antiatherogenic properties of HDL are largely attributed to this enzyme. There is an increasing need to represent a valid, reproducible, and reliable method to assay HDL function in routine clinical laboratories. In this context, HDL-associated proteins may be key players; notably PON1 activity (its arylesterase activity) may be a proper candidate because its decreased activity can be considered an important risk factor for HDL dysfunctionality. Of note, automated methods have been developed for the measurement of serum PON1 activity that facilitates its assay in large sample numbers. Arylesterase activity is proposed as a preferred activity among the different activities of PON1 for its assay in epidemiological studies. The binding of PON1 to HDL is critical for the maintenance of its activity and it appears apolipoprotein A-I plays an important role in HDL-PON1 interaction as well as in the biochemical and enzymatic properties of PON1. The interrelationships between HDL, PON1, and HDL's other components are complex and incompletely understood. The purpose of this review is to discuss biochemical and clinical evidence considering the interactions of PON1 with HDL and the role of this enzyme as an appropriate biomarker for HDL function as well as a potential therapeutic target.

Social inequalities in pregnancy metabolic profile: findings from the multi-ethnic Born in Bradford cohort study.

BACKGROUND: Lower socioeconomic position (SEP) associates with adverse pregnancy and perinatal outcomes and with less favourable metabolic profile in nonpregnant adults. Socioeconomic differences in pregnancy metabolic profile are unknown. We investigated association between a composite measure of SEP and pregnancy metabolic profile in White European (WE) and South Asian (SA) women. METHODS: We included 3,905 WE and 4,404 SA pregnant women from a population-based UK cohort. Latent class analysis was applied to nineteen individual, household, and area-based SEP indicators (collected by questionnaires or linkage to residential address) to derive a composite SEP latent variable. Targeted nuclear magnetic resonance spectroscopy was used to determine 148 metabolic traits from mid-pregnancy serum samples. Associations between SEP and metabolic traits were examined using linear regressions adjusted for gestational age and weighted by latent class probabilities. RESULTS: Five SEP sub-groups were identified and labelled 'Highest SEP' (48% WE and 52% SA), 'High-Medium SEP' (77% and 23%), 'Medium SEP' (56% and 44%) 'Low-Medium SEP' (21% and 79%), and 'Lowest SEP' (52% and 48%). Lower SEP was associated with more adverse levels of 113 metabolic traits, including lower high-density lipoprotein (HDL) and higher triglycerides and very low-density lipoprotein (VLDL) traits. For example, mean standardized difference (95%CI) in concentration of small VLDL particles (vs. Highest SEP) was 0.12 standard deviation (SD) units (0.05 to 0.20) for 'Medium SEP' and 0.25SD (0.18 to 0.32) for 'Lowest SEP'. There was statistical evidence of ethnic differences in associations of SEP with 31 traits, primarily characterised by stronger associations in WE women e.g., mean difference in HDL cholesterol in WE and SA women respectively (vs. Highest-SEP) was -0.30SD (-0.41 to -0.20) and -0.16SD (-0.27 to -0.05) for 'Medium SEP', and -0.62SD (-0.72 to -0.52) and -0.29SD (-0.40 to -0.20) for 'Lowest SEP'. CONCLUSIONS: We found widespread socioeconomic differences in metabolic traits in pregnant WE and SA women residing in the UK. Further research is needed to understand whether the socioeconomic differences we observe here reflect pre-conception differences or differences in the metabolic pregnancy response. If replicated, it would be important to explore if these differences contribute to socioeconomic differences in pregnancy outcomes.

High-density lipoprotein (HDL) as an indicator for alcohol use in a psychiatrically ill population.

AIMS: To examine the cross sectional and longitudinal associations between the Alcohol Use Disorders Identification Test-Concise (AUDIT-C) and differences in high-density lipoprotein (HDL) in a psychiatrically ill population. METHODS: Retrospective observational study using electronic health record data from a large healthcare system, of patients hospitalized for a mental health/substance use disorder (MH/SUD) from 1 July 2016 to 31 May 2023, who had a proximal AUDIT-C and HDL (N = 15 915) and the subset who had a repeat AUDIT-C and HDL 1 year later (N = 2915). Linear regression models examined the association between cross-sectional and longitudinal AUDIT-C scores and HDL, adjusting for demographic and clinical characteristics that affect HDL. RESULTS: Compared with AUDIT-C score = 0, HDL was higher among patients with greater AUDIT-C severity (e.g. moderate AUDIT-C score = 8.70[7.65, 9.75] mg/dl; severe AUDIT-C score = 13.02 [12.13, 13.90] mg/dL[95% confidence interval (CI)] mg/dl). The associations between cross-sectional HDL and AUDIT-C scores were similar with and without adjusting for patient demographic and clinical characteristics. HDL levels increased for patients with mild alcohol use at baseline and moderate or severe alcohol use at follow-up (15.06[2.77, 27.69] and 19.58[2.77, 36.39] mg/dL[95%CI] increase for moderate and severe, respectively). CONCLUSIONS: HDL levels correlate with AUDIT-C scores among patients with MH/SUD. Longitudinally, there were some (but not consistent) increases in HDL associated with increases in AUDIT-C. The increases were within range of typical year-to-year variation in HDL across the population independent of alcohol use, limiting the ability to use HDL as a longitudinal clinical indicator for alcohol use in routine care.

No effect of liraglutide on high density lipoprotein apolipoprotein AI kinetics in patients with type 2 diabetes.

AIM: The catabolism of high density lipoprotein (HDL) apolipoprotein AI (apoAI) is accelerated in patients with type 2 diabetes (T2D), related to hypertriglyceridemia, insulin resistance and low plasma adiponectin levels. Since liraglutide is likely to partly correct these abnormalities, we hypothesized that it might have a beneficial effect on HDL apoAI kinetics in patients with T2D. METHODS: An in vivo kinetic study of HDL apoAI was performed in 10 patients with T2D before and after 6 months of treatment with 1.2 mg/day of liraglutide, using a bolus of l-[1-13C]leucine followed by a 16-hour constant infusion. RESULTS: Liraglutide reduced BMI (34.9 ± 4.7 vs 36.6 ± 4.9 kg/m2, P = 0.012), HbA1c (7.1 ± 1.1 vs 9.6 ± 2.6%, P = 0.003), HOMA-IR (5.5 ± 1.9 vs 11.6 ± 11.2, P = 0.003), fasting triglycerides (1.76 ± 0.37 vs 2.48 ± 0.69 mmol/l, P < 0.001) and triglycerides during kinetics (2.34 ± 0.81 vs 2.66 ± 0.65 mmol/l, P = 0.053). Plasma HDL cholesterol and adiponectin concentrations were unchanged (respectively 0.97 ± 0.26 vs 0.97 ± 0.19 mmol/l, P = 1; 3169 ± 1561 vs 2618 ± 1651 µg/l, P = 0.160), similar to triglyceride content in HDL (5.13 ± 1.73 vs 5.39 ± 1.07%, P = 0.386). Liraglutide modified neither HDL apoAI fractional catabolic rate (0.35 ± 0.11 vs 0.38 ± 0.11 pool/day, P = 0.375), nor its production rate (0.44 ± 0.13 vs 0.49 ± 0.15 g/l/day, P = 0.375), nor its plasma concentration (1.26 ± 0.19 vs 1.29 ± 0.14 g/l, P = 0.386). CONCLUSION: Six months of treatment with 1.2 mg/day of liraglutide had no effect on the kinetics of HDL apoAI in patients with T2D. The lack of decrease in triglyceride content in HDL related to an only moderate decrease in triglyceridemia, probably greatly explains these results. Insufficient improvement of insulin sensitivity and adiponectinemia may also be implied.

The association between monocyte-to-high-density lipoprotein ratio and hyperuricemia: Results from 2009 to 2018.

Previous research has suggested that the monocyte-to-high-density lipoprotein ratio (MHR), an emerging inflammatory biomarker, holds promise in predicting the prevalence of various cardiovascular and metabolic diseases. However, earlier investigations were constrained by the relatively modest sample sizes. This study endeavored to expand the sample size and conduct a more comprehensive exploration of the potential relationship between MHR and hyperuricemia. This cross-sectional study incorporated data from participants of the 2009 to 2018 National Health and Nutrition Examination Survey (NHANES) with complete and qualifying information. MHR was determined by calculating the ratio between monocyte count and high-density lipoprotein levels. Various statistical methodologies such as weighted multivariate logistic regression, subgroup analysis, smoothed curve fitting, and threshold analysis, have been used to explore the correlation between hyperuricemia and MHR. The study included a cohort of 17,694 participants, of whom 3512 were diagnosed with hyperuricemia. MHR levels were notably higher in the hyperuricemia group than in the normal group, aligning with an elevated body mass index (BMI). A comprehensive multivariate logistic analysis, accounting for all relevant adjustments, revealed a notable positive correlation between MHR and hyperuricemia (P < .001, OR = 1.98, 95% CI: 1.54-2.54). Subgroup analysis indicated that the MHR exhibited an enhanced predictive capacity for identifying hyperuricemia risk, particularly in females (P < .05). Curvilinear and threshold analyses revealed a nonlinear association between MHR and hyperuricemia prevalence, with a notable inflection point at 0.826. In the US population, a clear positive correlation was observed between the MHR and prevalence of hyperuricemia. Importantly, the MHR is a more robust predictor of hyperuricemia risk in females. Further investigations are required to confirm these findings.